Effects of CNS Hypoxia

Manifestations of CNS-Mediated Respiratory Depressant Effects of Hypoxia 

Conceptually, the most straightforward way to demonstrate the ventilatory effects of brain hypoxia is to expose peripherally chemodenervated animals to a hypoxic environment. The results of sueh studies, however, are not uniform with the major eonfounding variable being arousal state. In awake, unanaesthetized, chemodenervated animals both exeitation and depression have been reported (as reviewed in Ref 2). The response most often observed consists of tachypnea with variable effects on tidal volume and httle or no ehange in alveolar ventilation. In one study, the tachypnea was related to an inerease in systemic metabolic rate and reversed by adrenergic blockade (3). 

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Assoeiated with poststimulus excitation of phrenic nerve amplitude is a deeline below baseline of respiratory frequency. Recent studies suggest that posthypoxie frequency decline, which is seen in the carotid sinus intact animal, may be mediated in the ventrolateral pons (17,18), and that the phenomenon appears to require NMDA receptor activation (19). 

A much-studied respiratory depressant effect of hypoxia that is either directly or indirectly mediated by the CNS has been termed hypoxic ventilatory decline. That the ventilatory deeline with arterial hypoxia in carotid sinus nerve (CSN) denervated anesthetized eats with maintained arterial Pco2 could be reversed by electrical stimulation of the eut CSN suggests that the CSN input maintained ventilation with eoneomitant central nervous system (CNS) hypoxic depression (19a). This evidenee also suggests that hypoxic CNS inhibition is an active process (see later. Refs. 2,4,11). In adult humans and some animals, when isocapnic hypoxia is produced in a square-wave fashion, the initial enhancement of respiratory output is followed, in about 5-7 min, by a decline to approximately 50% of the peak level (20-22). The phenomenon is best observed in the imanaesthetized state, but may be seen in anesthetized animals as well. It is far more prominent in the early neonate (1-5 days in humans) where the decline in respiratory output may be to baseline or below the initial level of respiratory output. Recent studies in the neonate have demonstrated a significant genetic variation to expression of this phenomenon (23). 

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It is the thesis of this review that for the most part, both the excitatory and depressant ventilatory effects of CNS hypoxia are specific adaptive processes, phylogeneticaUy and perhaps ontologicaUy conserved, rather than nonspecific events brought about by insufficient substrate availability for neuronal energy metabolism. 

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